The transdermal route of parenteral delivery of drugs provides many advantages and transdermal systems for delivering a wide variety of drugs or other beneficial agents are described in U.S. Pat. Nos. 3,598,122, 3,598,123, 4,379,454, 4,286,592, 4,314,557 and 4,568,343 for example, all of which are incorporated herein by reference. In many cases, drugs which would appear to be ideal candidates for transdermal delivery are found to have such low permeability through intact skin that they cannot be delivered at therapeutically effective rates from reasonably sized systems. In an effort to increase skin permeability it has been proposed to pretreat the skin with various chemicals or to concurrently deliver the drug in the presence of a permeation enhancer. Various materials have been suggested for this purpose as described in U.S. Pat. Nos. 4,299,826, 4,343,798, 4,046,886, 4,130,643, 4,405,616, 4,335,115, 4,130,667, 3,903,256, 4,379,454, 3,527,864, 3,952,099, 3,896,238, 3,472,931 all of which are incorporated herein by reference, British Pat. No. 1,001,949 and Idson, Percutaneous Absorption, J. Phar. Sci., Vol. 64, No. b6, June 1975, pp. 901-924 (particularly 919-921). To be considered useful a permeation enhancer should possess certain characteristics in addition to its ability to enhance the permeability of at least one and preferably a large number of drugs. These characteristics include being non-toxic, non-irritating on prolonged exposure and under occlusion, and non-sensitizing on repeated exposure. Preferably it should also be odorless and capable of delivering drugs without producing burning or tingling sensations.
According to our invention, we have discovered that sucrose esters and in particular sucrose monolaurate (SML), are effective in enhancing the permeation of several drugs and other therapeutic or beneficial agents through body surfaces and membranes, generally, and skin, particularly, and when formulated in pharmaceutical compositions with other materials appears to satisfy the criteria noted above.
As noted above, the preferred sucrose ester is SML. It has been determined that the C.sub.12 ester is most useful. For the sucrose esters, the C.sub.12 is sucrose monolaurate. Alternately, instead of using SML alone, mixtures of the sucrose esters of coconut fatty acids, which are predominantly comprised of SML are also suitable. A readily available source of one such SML predominating mixture is SUCROSE MONOCOCOATE, commercially available from Croda, Inc. (New Jersey), which is an ester mixture, with C.sub.12 predominating.
It is accordingly an object of our invention to increase the permeability of body surfaces of animals and humans, including the mucosa and other membranes and more particularly of human skin, to the transport of drugs and other beneficial agents by the concurrent application of the drug or beneficial agent and SML to the body surface.
It is another object of our invention to provide compositions of matter for application to the skin which comprise SML and a transdermally deliverable drug or beneficial agent.
It is another object of our invention to provide transdermal therapeutic systems for the concurrent delivery of SML and a drug or beneficial agent.